Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study

Chun-Hsin Chen; Chih-Chiang Chiu; Yi-Hang Chiu; Chin-Hao Chang; Yu-Han Chang; Ming-Chyi Huang; Mong-Liang Lu; Po-Yu Chen

doi:10.1016/j.jfma.2024.11.019

Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study

J Formos Med Assoc. 2024 Dec 7:S0929-6646(24)00556-4. doi: 10.1016/j.jfma.2024.11.019. Online ahead of print.

Authors

Chun-Hsin Chen¹, Chih-Chiang Chiu², Yi-Hang Chiu³, Chin-Hao Chang⁴, Yu-Han Chang⁴, Ming-Chyi Huang⁵, Mong-Liang Lu⁶, Po-Yu Chen⁷

Affiliations

¹ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
² Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.
³ Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
⁶ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁷ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: [email protected].

PMID: 39645464
DOI: 10.1016/j.jfma.2024.11.019

Abstract

Purpose: We aimed to evaluate the effects of folate and vitamin B12 on psychopathology in patients with schizophrenia and low serum folate levels.

Methods: Fifty-five schizophrenia patients with serum folate levels lower than 6 mg/L were randomized in a 2:1 ratio to supplementation with 5 mg of folate and 500 μg of vitamin B12 per day (the folate group, n = 36) or placebo (the placebo group, n = 19) for 24 weeks. We evaluated patients' symptomatology with the Positive and Negative Symptom Scale (PANSS) and cognitive functions with Cogstate.

Results: During the 24-week intervention, serum folate and vitamin B12 levels significantly increased, and homocysteine level significantly decreased in the folate group, but these markers did not significantly change in the placebo group. There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups. A subgroup analysis within the folate groups revealed no significant differences in the changes of psychotic symptoms severity or cognitive functions among patients with different degrees of folate level increments.

Conclusion: Our finding suggested that the extent of increased folate levels did not exert a notable impact on the changes of psychotic symptoms severity or cognitive function in our patients. It may also due to the relatively stable condition in our recruited patients, so supplementation of folate cannot show its effectiveness. Whether folate can improve psychopathology in moderate to severe patients with schizophrenia should be evaluated with a larger sample size in the future.

Keywords: Cognitive functions; Folate; One-carbon metabolism; Psychopathology; Schizophrenia.